Key Takeaways of new insulin products Sara Wettergreen PharmD BCACP Assistant Professor of Pharmacotherapy University of North Texas System College of Pharmacy Learning Objectives Pharmacists ID: 573095
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Slide1
Concentrate!Key Takeaways of new insulin products
Sara Wettergreen,
PharmD
, BCACP
Assistant Professor of Pharmacotherapy
University of North Texas System College of PharmacySlide2
Learning Objectives: Pharmacists
Compare and contrast use of insulin pen devices
Identify patients who may benefit from use of new insulin products
Design a patient-specific treatment regimen using new insulin products Slide3
Learning Objectives: Technicians
Compare and contrast use of insulin pen devices
Define safety considerations related to insulin use
Assist patients with obtaining pricing discounts for new insulin productsSlide4
Diabetes: A Growing Problem
Center
for Disease Control (CDC). National diabetes statistics report, 2014.
29.1 million people in the United States have diabetes
About 1 in 4 of these are undiagnosed
37% of patients treated for diabetes use insulin Slide5
“Egregious Eleven”
Schwartz et al.
Dia
Care 2016;39:179-186Slide6
Role of Insulin
American Diabetes Association
Dia
Care 2016;39:S52-S59Slide7
Role of Insulin
Reprinted with permission from American Association of Clinical Endocrinologists © 2016 AACE.
Endocr
Pract.2016;22: 84-113.Slide8
New Insulin Products
Insulin glargine U-100 equivalent (
Basaglar
®)
Became available December 15
th
, 2016
Insulin glargine U-300 (Toujeo®)Insulin degludec U-100 and U-200 (Tresiba®) Regular human insulin u-500 (Humulin R U-500 KwikPen®)Insulin lispro U-200 (Humalog U-200 KwikPen®)www.accessdata.fda.gov/Scripts/cder/drugsatfda/ .Slide9
PK/PD profile that more closely mimics endogenous basal insulin secretion
Low risk of hypoglycemia
Minimal weight gain
Dosing flexibility
Easy for patients to administer
Characteristics of an Ideal Basal InsulinSlide10
Advances with Basal Insulins
NPH
Peak
Shorter duration
Risk of hypoglycemia
Detemir
Glargine U-100
Glargine U-100 equivalentLess peakLonger durationLower risk of hypoglycemia
Glargine U-300Degludec U-100, U-200
Less peak
Longer duration
Lower risk of hypoglycemiaSlide11
Insulin Glargine U-100 Equivalent (Basaglar®)
Not considered a “biosimilar” as the Biologic License Application (BLA) pathway was not used, but is a follow-on biologic approved via the New Drug Application (NDA) pathway
Conversion from insulin glargine U-100 (Lantus®) is 1:1 dose
Non-inferior to insulin glargine U-100 (Lantus®)
Basaglar [Prescribing Information]. Indianapolis, IN: Eli Lilly and Company.
Rosenstock J, et al. Diabetes Obes Metab. 2015;17(8):734-741.Slide12
FDA approved February 2015Available in disposable, prefilled SoloSTAR pen device
1/3 of injection volume compared with U-100
Reduces depot surface area by ½
Allows for a gradual, prolonged rate of absorption
Each pen contains
450 units
Maximum single injection dose =
80 unitsInsulin Glargine U-300 (Toujeo®) U-100 U-300Surface AreaVolume
TOUJEO® (insulin glargine) injection 300 units/mL [prescribing information]. Bridgewater, NJ: Sanofi-Aventis.Slide13
Becker RHA. Diabetes Care 2015;38:637-43.
PK/PD of Insulin Glargine U-300 vs. U-100Slide14
EDITION 1: Insulin Glargine U-300
Riddle MC. Diabetes Care 2014;37:2755-62
.
Multicenter, open-label
T2D patients, A1C 7%–10%
Current basal therapy with ≥ 42 units/day of glargine or NPH + mealtime RAIA ± metformin
Insulin glargine U-300
Once daily using pen deviceAdjusted no more than every 3 days to goal FPG 80–100 mg/dLInsulin glargine U-100Once daily using pen deviceAdjusted no more than every 3 days to goal FPG 80–100 mg/dLPrimary Outcome: A1C change from baseline to month 6Slide15
EDITION 1: Insulin Glargine U-300
Riddle MC. Diabetes Care 2014;37:2755-62.
Outcome
Glargine U-300
(n=404)
Glargine
U-100(n=403)Change in A1C from baseline (%)-0.83-0.83Change in weight from baseline (kg)+0.9+0.9Daily basal insulin dose at end of study (units)10394Confirmed or severe nocturnal hypoglycemic events (%)
36
46
Met predefined noninferiority criteria.Slide16
EDITION 2: Insulin Glargine U-300
Yki-Jarvinen
H. Diabetes Care 2014;37:3235-43.
Multicenter, open-label
T2D patients, A1C 7%–10%
Current basal therapy with ≥ 42 units/day of glargine or NPH + OADs
Insulin glargine U-300
Once daily using pen deviceAdjusted no more than every 3 days to goal FPG 80–100 mg/dLInsulin glargine U-100Once daily using pen deviceAdjusted no more than every 3 days to goal FPG 80–100 mg/dLPrimary Outcome: A1C change from baseline to month 6Slide17
EDITION 2: Insulin Glargine U-300
Outcome
Glargine U-300
(n=404)
Glargine
U-100
(n=407)Change in A1C from baseline (%)-0.57-0.56Daily basal insulin dose at end of study (units)9182Nocturnal hypoglycemic (%)30.541.6Confirmed or severe hypoglycemia (%)21.627.9
Met predefined noninferiority criteria.
Yki-Jarvinen
H. Diabetes Care 2014;37:3235-43.Slide18
EDITION 3: Insulin Glargine U-300
Multicenter, open-label
T2D patients, A1C 7%–11%
Insulin naive using OADs
Insulin glargine U-300
Once daily using pen device
Adjusted no more than every 3 days to goal FPG 80–100 mg/dL
Insulin glargine U-100Once daily using pen deviceAdjusted no more than every 3 days to goal FPG 80–100 mg/dLPrimary Outcome: A1C change from baseline to month 6Bolli GB. Diabetes Obes Metab 2015;17:386-94.Slide19
EDITION 3: Insulin Glargine U-300
Outcome
Glargine U-300
(n=439)
Glargine
U-100
(n=439)Change in A1C from baseline (%)-1.42-1.46Daily basal insulin dose at end of study (units)59.452Nocturnal confirmed or severe hypoglycemic (%)1824Met predefined noninferiority criteria.
Bolli GB. Diabetes Obes Metab 2015;17:386-94.Slide20
Insulin Glargine U-300: Summary
Smoother PK/PD profile than
glargine
U-100
Full 24-hour coverage; flexibility in dosing time
Less nocturnal hypoglycemia than
glargine
U-100Smaller injection volume1:1 conversion recommended when switching from glargine U-100Higher doses (~10%) may be needed compared with insulin glargine U-100TOUJEO® (insulin glargine) injection 300 units/mL [prescribing information]. Bridgewater, NJ: Sanofi-Aventis.Slide21
Approved by FDA September 25, 2015U-100 (Tresiba® 100 units/mL)
FlexTouch pen device
300 units per pen; max single dose =
80 units
Duration of action > 40 hours; allows for flexibility in dosing
Doses are selected in
1 unit
incrementsU-200 (Tresiba® 200 units/mL)FlexTouch pen device; low volume600 units per pen, max single dose = 160 unitsBioequivalent to degludec U-100; similar glucose loweringDoses are selected in 2 unit increments Insulin Degludec (Tresiba®)Zinman B. Diabetes Care 2012;35:2464-71; Gough SC. Diabetes Care 2013;36:2536-42Garber AJ. Lancet 2012;379:1498-507. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm464321.htmSlide22
Insulin Degludec PK/PD
Half life >25 hours
Duration of action: 42 hours
Steady state is reached within 3 days, thus dose titrations should occur on a weekly basis
Similar PK/PD between the U-100 and U-200 concentrations
Vora
J, et al. Diabetes Research in Clinical Practice 2015;109:19-31. Slide23
Insulin Degludec
Clinical
Trial (Duration)
Background
Therapy
Comparator Arms
Change in A1C (%)
End of Trial Insulin Dose (units/kg)Hypo-glycemia (episodes per pt-year)Confirmed or Severe Nocturnal Hypoglycemia (per pt-year)Zinman(52 weeks)Metformin (insulin naive)
IDeg
U-100
-1.06
0.59
1.52
0.25*
Glargine
-1.19
0.60
1.85
0.39
Garber
(52 weeks)
Insulin ± OADs
IDeg U-100
-1.1
0.75
11.1*
1.4*
Glargine
-1.2
0.69
13.6
1.8
Gough
(26 weeks)
Metformin ± DPP-4i
(insulin naive)
IDeg
U-200
-1.22
0.53*
1.22
0.18
Glargine
-1.42
0.60
1.42
0.28
Noninferiority criteria met.
*p<0.05.
Zinman
B. Diabetes Care 2012;35:2464-71; Gough SC. Diabetes Care 2013;36:2536-42; Garber AJ. Lancet 2012;379:1498-507.Slide24
Converting to Insulin
Degludec
Vora
J, et al. Diabetes Research in Clinical Practice 2015;109:19-31. Slide25
Titration Frequency
TITRATE Study: Insulin
determir
was titrated by 3 units every 3 days
Titrations with insulin
degludec
should be made on a weekly basis due to the extended duration of action
AdherenceFlexibility in timing between doses with a minimum of 8 hours between dosesMinimal change is safety or efficacy with variability in timing of doses between 8 to 40 hours between dosesPatient Considerations with Insulin DegludecVora J, et al. Diabetes Research in Clinical Practice 2015;109:19-31. Slide26
Insulin Degludec: Summary
Extended duration of action compared to other basal insulin products
Less nocturnal hypoglycemia with
degludec
U-100 than glargine U-100
1:1 conversion recommended when switching from other basal insulins
20% dose reduction may be considered if using twice daily dosing
Extended coverage; flexibility in dosing time; weekly titrationsVora J, et al. Diabetes Research in Clinical Practice 2015;109:19-31. Slide27
Regular Human Insulin U-500 (Humulin R U-500
KwikPen
®)
Nothing new about the
insulin
Five times as concentrated as U-100 insulin
Used for severe insulin resistance (total daily dose >200 units/day)
The PEN is new!1500 units per 3 mL penDoses are selected in 5 unit increments No dose-conversions needed (compared to vial use)Humulin R U-500 KwikPen [Prescribing Information]. Indianapolis, IN: Eli Lilly and Company.Slide28
Continues to be available in a 20 mL vial (10,00 units of insulin)U-500 syringe is recommended for use with the U-500 vial
Regular Human Insulin U-500
Humulin R U-500 [Prescribing Information]. Indianapolis, IN: Eli Lilly and Company.Slide29
Regular Human Insulin U-500: Dosing Review
Conversion from U-100 products to U-500
A1c ≥ 8%: 1:1 conversion from U-100 to U-500 insulin total daily dose (TDD)
May decrease TDD by 10-20% if A1c<8%
The TDD is then divided
Required TDD (Units)
Route and Frequency
U-500 Insulin Dosage150-300Twice daily50/50 or 60/40 before breakfast and supperThree times daily33/33/33 before meals300-600
Three times daily
33/33/33 before meals
Four times
daily
30/30/30/10 (mealtimes and bedtime)
>600
Four times daily
30/30/30/10 (mealtimes and bedtime)
Segal AR, et al. Am J Health-
Syst
Pharm. 2010; 67:1526-35Slide30
Regular Human Insulin U-500: Dose Titration
Ballani
P, et al. Diabetes Care. 2006; 29(11):2504-2505.Slide31
Low risk of hypoglycemia
Minimal weight gain
Dosing flexibility
Easy for patients to administer
Characteristics of an Ideal Bolus InsulinSlide32
Advances with Bolus Insulins
Regular
Slow onset
Longer duration
Risk of hypoglycemia
Rapid-acting insulin analogs
Faster onset
Shorter durationClinical outcomesPen devicesLispro U-200
Decreased number of pens needed with high doses
Pen deviceSlide33
Insulin Lispro U-200 (Humalog U-200
KwikPen
®)
The CONCENTRATION is new!
Twice as concentrated as U-100 insulin
1500 units per 3 mL pen
Doses are selected in
1 unit increments 1:1 unit conversion recommend when switching from insulin lispro U-100Benefit is that patients on high bolus doses will use less pensHumalog [Prescribing Information]. Indianapolis, IN: Eli Lilly and Company.http://www.humalog.com/humalog-u200-hcp.aspxSlide34
Ultra-Rapid Acting Insulin Aspart
(NN1218)
Earlier time to 50% maximal concentration
Faster-acting insulin
aspart
: 20.7 minutes
Insulin
aspart: 31.6 minutes Application submitted to the FDAOctober 7, 2016 – FDA response letter issued requesting additional information for the immunogenicity and clinical pharmacology data Heise T, et al. Diabetes Obes Metab. 2015;17(7):682-688http://www.novonordisk.com/media/news-details.2047717.htmlSlide35
Discussion Question!
What patients may be good candidates for each of these new insulin products?
Insulin glargine U-300 (
Toujeo
®)
Insulin
degludec
U-100 and U-200 (Tresiba®) Regular human insulin u-500 (Humulin R U-500 KwikPen®)Insulin lispro U-200 (Humalog U-200 KwikPen®)Slide36
Cost Considerations
Insulin product
How supplied
Total units/pen
Cost
Cost/unit
Insulin glargine U-300
1.5 mL pens450$134$0.30Insulin glargine U-100 3 mL pens300$89$0.30Insulin glargine U-100 equivalent3 mL pens300TBDTBDInsulin
degludec U-200
3 mL pens
600
$213
$0.36
Insulin
degludec
U-100
3 mL pens
300
$107
$0.36
Regular human insulin
U-500 pen
3 mL pens
1,500
$320
$0.21
Regular human insulin U-500 vial
20 mL vial
10,000
$1655
$0.16
Insulin
lispro
U-200
3 mL pens
600
$236
$0.39
Insulin
lispro
U-100
3 mL
pens
300
$118
$0.39
Table adapted from:
Mospan
CM.JAAPA. 2016; 29(6):16-18;
Pricing from
www.lexicomp.com
as of October 2016Slide37
Drug Discount Programs
Insulin product
Program
Details
Insulin glargine U-300
Discount cards are available
Card can reduce copay to $15, with a maximal discount of $200/pack
Can be used for the first 12 prescription fillsSanofi Patient Connection Program May be able to decrease drug price to $0 copayInsulin degludec U-200/U-100Discount cards are availableCan decrease copayment to as low as $15 (maximal discount of $500 for each fill)Can be used for the first 24 prescription fillsRegular human insulin U-500 penDiscount cards availableCard can reduce copay
to $25, with a maximum of 7 KwikPen packs per prescription fills
Can be used for the first 12 prescription fills
Insulin
lispro
U-200
Discount cards available
Can decrease copayment to as low as $25 (maximal discount of $100 for each fill)
Can be used for the first 24 prescription fills
www.toujeo.com
;
www.tresiba.com
;
www.humulin.com
;
www.humalog.com
; Slide38
Not Just an Outpatient Issue!
In the Inpatient Setting:
Insulin pens are preferred by nurses
Felt it was easier to teach patients to self-administer insulin using a pen device
Felt that the risk of a dosing error was lower with a pen device vs. syringe
Reduced waste from using insulin pens instead of vials may reduce cost
One study projected a cost savings of
$36 per patient per hospital stay with insulin pen use instead of insulin vialsHaines ST, et al. Am J Health-Syst Pharm. 2016; 73(suppl 5):S4-16.Slide39
A Risky Situation…
2009:
At a Texas hospital in 2009, 2,114 insulin-dependent patients with diabetes were exposed to disease transmission risk via used insulin pens
2011:
Over 2,000 patients were exposed to used insulin pens at a Wisconsin hospital and outpatient clinic
2013:
Over 700 patients at a New York hospital may have been exposed inadvertently to human immunodeficiency virus (HIV), hepatitis B, or hepatitis C because of the reuse of insulin pens on multiple patients
http://www.ismp.org/newsletters/acutecare/showarticle.aspx?id=41Slide40
Discussion Question!
Are insulin pens used at your practice site?
If so, how do you decrease the risk of reusing insulin pens?Slide41
Best Practices for Safe Use of Insulin Pen Devices in Hospitals
Recommendations have been made for each step in the medication-use process
Examples:
“Warning! Confirm patient. Insulin pens are for use in one patient only”
Require all health professionals to pass a competency assessment for insulin pens (at the time of hire and periodically thereafter)
Develop a system to prompt the proper disposal of insulin pens when the order is discontinued
Haines ST, et al. Am J Health-
Syst Pharm. 2016; 73(suppl 5):S4-16.Slide42
Key Takeaways
37% of patients treated for diabetes use insulin
Many new insulin products are available, each with their own advantages
Cost may be a barrier to patient use, and drug discount programs are one method of assisting patients reduce costs
Addition of new insulin products can lead to further confusion with the various devices available, which has implications for both the inpatient and outpatient settings Slide43
Concentrate! Key Takeaways of new insulin products
Sara Wettergreen,
PharmD
, BCACP
Assistant Professor of Pharmacotherapy
University of North Texas System College of Pharmacy